A refined analysis of Neanderthal-introgressed sequences in modern humans with a complete reference genome
Abstract Background Leveraging long-read sequencing technologies, the first complete human reference genome, T2T-CHM13, corrects assembly errors in previous references and resolves the remaining 8% of the genome. While studies on archaic admixture in modern humans have so far relied on the GRCh37 re...
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2025-02-01
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| Series: | Genome Biology |
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| Online Access: | https://doi.org/10.1186/s13059-025-03502-z |
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| author | Shen-Ao Liang Tianxin Ren Jiayu Zhang Jiahui He Xuankai Wang Xinrui Jiang Yuan He Rajiv C. McCoy Qiaomei Fu Joshua M. Akey Yafei Mao Lu Chen |
| author_facet | Shen-Ao Liang Tianxin Ren Jiayu Zhang Jiahui He Xuankai Wang Xinrui Jiang Yuan He Rajiv C. McCoy Qiaomei Fu Joshua M. Akey Yafei Mao Lu Chen |
| author_sort | Shen-Ao Liang |
| collection | DOAJ |
| description | Abstract Background Leveraging long-read sequencing technologies, the first complete human reference genome, T2T-CHM13, corrects assembly errors in previous references and resolves the remaining 8% of the genome. While studies on archaic admixture in modern humans have so far relied on the GRCh37 reference due to the availability of archaic genome data, the impact of T2T-CHM13 in this field remains unexplored. Results We remap the sequencing reads of the high-quality Altai Neanderthal and Denisovan genomes onto GRCh38 and T2T-CHM13. Compared to GRCh37, we find that T2T-CHM13 significantly improves read mapping quality in archaic samples. We then apply IBDmix to identify Neanderthal-introgressed sequences in 2504 individuals from 26 geographically diverse populations using different reference genomes. We observe that commonly used pre-phasing filtering strategies in public datasets substantially influence archaic ancestry determination, underscoring the need for careful filter selection. Our analysis identifies approximately 51 Mb of Neanderthal sequences unique to T2T-CHM13, predominantly in genomic regions where GRCh38 and T2T-CHM13 assemblies diverge. Additionally, we uncover novel instances of population-specific archaic introgression in diverse populations, spanning genes involved in metabolism, olfaction, and ion-channel function. Finally, to facilitate the exploration of archaic alleles and adaptive signals in human genomics and evolutionary research, we integrate these introgressed sequences and adaptive signals across all reference genomes into a visualization database, ASH ( www.arcseqhub.com ). Conclusions Our study enhances the detection of archaic variations in modern humans, highlights the importance of utilizing the T2T-CHM13 reference, and provides novel insights into the functional consequences of archaic hominin admixture. |
| format | Article |
| id | doaj-art-88155ea2c631441483ad5efbf57ceb9e |
| institution | DOAJ |
| issn | 1474-760X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj-art-88155ea2c631441483ad5efbf57ceb9e2025-08-20T03:10:52ZengBMCGenome Biology1474-760X2025-02-0126112010.1186/s13059-025-03502-zA refined analysis of Neanderthal-introgressed sequences in modern humans with a complete reference genomeShen-Ao Liang0Tianxin Ren1Jiayu Zhang2Jiahui He3Xuankai Wang4Xinrui Jiang5Yuan He6Rajiv C. McCoy7Qiaomei Fu8Joshua M. Akey9Yafei Mao10Lu Chen11State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, School of Life Science, Fudan UniversityBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong UniversityState Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, School of Life Science, Fudan UniversityMinistry of Education Key Laboratory of Contemporary Anthropology, Center for Evolutionary Biology, School of Life Science, Fudan UniversityBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong UniversityBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong UniversityMinistry of Education Key Laboratory of Contemporary Anthropology, Center for Evolutionary Biology, School of Life Science, Fudan UniversityDepartment of Biology, Johns Hopkins UniversityKey Laboratory of Vertebrate Evolution and Human Origins, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of SciencesThe Lewis-Sigler Institute for Integrative Genomics, Princeton UniversityBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong UniversityState Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, School of Life Science, Fudan UniversityAbstract Background Leveraging long-read sequencing technologies, the first complete human reference genome, T2T-CHM13, corrects assembly errors in previous references and resolves the remaining 8% of the genome. While studies on archaic admixture in modern humans have so far relied on the GRCh37 reference due to the availability of archaic genome data, the impact of T2T-CHM13 in this field remains unexplored. Results We remap the sequencing reads of the high-quality Altai Neanderthal and Denisovan genomes onto GRCh38 and T2T-CHM13. Compared to GRCh37, we find that T2T-CHM13 significantly improves read mapping quality in archaic samples. We then apply IBDmix to identify Neanderthal-introgressed sequences in 2504 individuals from 26 geographically diverse populations using different reference genomes. We observe that commonly used pre-phasing filtering strategies in public datasets substantially influence archaic ancestry determination, underscoring the need for careful filter selection. Our analysis identifies approximately 51 Mb of Neanderthal sequences unique to T2T-CHM13, predominantly in genomic regions where GRCh38 and T2T-CHM13 assemblies diverge. Additionally, we uncover novel instances of population-specific archaic introgression in diverse populations, spanning genes involved in metabolism, olfaction, and ion-channel function. Finally, to facilitate the exploration of archaic alleles and adaptive signals in human genomics and evolutionary research, we integrate these introgressed sequences and adaptive signals across all reference genomes into a visualization database, ASH ( www.arcseqhub.com ). Conclusions Our study enhances the detection of archaic variations in modern humans, highlights the importance of utilizing the T2T-CHM13 reference, and provides novel insights into the functional consequences of archaic hominin admixture.https://doi.org/10.1186/s13059-025-03502-zT2T-CHM13Archaic admixtureAdaptive introgressionDatabaseComplete human genome sequence |
| spellingShingle | Shen-Ao Liang Tianxin Ren Jiayu Zhang Jiahui He Xuankai Wang Xinrui Jiang Yuan He Rajiv C. McCoy Qiaomei Fu Joshua M. Akey Yafei Mao Lu Chen A refined analysis of Neanderthal-introgressed sequences in modern humans with a complete reference genome Genome Biology T2T-CHM13 Archaic admixture Adaptive introgression Database Complete human genome sequence |
| title | A refined analysis of Neanderthal-introgressed sequences in modern humans with a complete reference genome |
| title_full | A refined analysis of Neanderthal-introgressed sequences in modern humans with a complete reference genome |
| title_fullStr | A refined analysis of Neanderthal-introgressed sequences in modern humans with a complete reference genome |
| title_full_unstemmed | A refined analysis of Neanderthal-introgressed sequences in modern humans with a complete reference genome |
| title_short | A refined analysis of Neanderthal-introgressed sequences in modern humans with a complete reference genome |
| title_sort | refined analysis of neanderthal introgressed sequences in modern humans with a complete reference genome |
| topic | T2T-CHM13 Archaic admixture Adaptive introgression Database Complete human genome sequence |
| url | https://doi.org/10.1186/s13059-025-03502-z |
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